| Literature DB >> 26284498 |
Edina Lump1, Laura M Castellano2,3, Christoph Meier4, Janine Seeliger5, Nelli Erwin5, Benjamin Sperlich5, Christina M Stürzel1, Shariq Usmani1, Rebecca M Hammond2,6, Jens von Einem7, Gisa Gerold8, Florian Kreppel9, Kenny Bravo-Rodriguez10, Thomas Pietschmann8, Veronica M Holmes11, David Palesch1, Onofrio Zirafi1, Drew Weissman11, Andrea Sowislok12, Burkhard Wettig12, Christian Heid12, Frank Kirchhoff1,13, Tanja Weil4,13, Frank-Gerrit Klärner14, Thomas Schrader12, Gal Bitan15,16,17, Elsa Sanchez-Garcia10, Roland Winter5, James Shorter2,3, Jan Münch1,13.
Abstract
Semen is the main vector for HIV transmission and contains amyloid fibrils that enhance viral infection. Available microbicides that target viral components have proven largely ineffective in preventing sexual virus transmission. In this study, we establish that CLR01, a 'molecular tweezer' specific for lysine and arginine residues, inhibits the formation of infectivity-enhancing seminal amyloids and remodels preformed fibrils. Moreover, CLR01 abrogates semen-mediated enhancement of viral infection by preventing the formation of virion-amyloid complexes and by directly disrupting the membrane integrity of HIV and other enveloped viruses. We establish that CLR01 acts by binding to the target lysine and arginine residues rather than by a non-specific, colloidal mechanism. CLR01 counteracts both host factors that may be important for HIV transmission and the pathogen itself. These combined anti-amyloid and antiviral activities make CLR01 a promising topical microbicide for blocking infection by HIV and other sexually transmitted viruses.Entities:
Keywords: HIV; amyloid; biochemistry; biophysics; human; molecular tweezer; structural biology; viruses
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Year: 2015 PMID： 26284498 PMCID： PMC4536748 DOI： 10.7554/eLife.05397
Source DB: PubMed Journal: Elife ISSN： 2050-084X Impact factor: 8.140